About Me

My mother was murdered by what I call corporate and political homicide i.e. FOR PROFIT! she died from a rare phenotype of CJD i.e. the Heidenhain Variant of Creutzfeldt Jakob Disease i.e. sporadic, simply meaning from unknown route and source. I have simply been trying to validate her death DOD 12/14/97 with the truth. There is a route, and there is a source. There are many here in the USA. WE must make CJD and all human TSE, of all age groups 'reportable' Nationally and Internationally, with a written CJD questionnaire asking real questions pertaining to route and source of this agent. Friendly fire has the potential to play a huge role in the continued transmission of this agent via the medical, dental, and surgical arena. We must not flounder any longer. ...TSS

Sunday, April 27, 2008

I thought this most important research by Aguzzi et al 'Association between Deposition of Beta-Amyloid and Pathological Prion Protein in Sporadic Creutzfeldt-Jakob Disease' most important, and thought further reading of this study should be at hand. It seems that more research is further showing that the infamous 'one-in-a-million' diagnosis of CJD that was and is quoted all the time, and or the recently revised guess of 'one case per 9000 in adults age 55 and older', is dreadfully low and inaccurate, thus causing the potential for further exposure and transmission via the medical, surgical, and dental routes. for this reason it is paramount that all TSE be made reportable of all age groups, in every state. it must be made reportable nationally and internationally. also, I think it most important to further research the transmission of Alzheimer's disease, and find out if there is a risk of transmission via the proven routes as the TSE i.e. consumption, medical, surgical, dental, and if so, there may be a need to make Alzheimer's disease a reportable disease as well. ...TSS

PLEASE note, in my ignorance, and my machines, a few LETTERS/SYMBOLS describing B -amyloid (A B ) and apolipoprotein E e 4 will not be displayed properly i.e. the 'B' and the 'e' ...TSS

Association between Deposition of Beta-Amyloid and Pathological Prion Protein in Sporadic Creutzfeldt-Jakob Disease

Background: Alzheimer’s disease (AD) and prion diseases such as sporadic Creutzfeldt-Jakob disease (sCJD) share common features concerning their molecular pathogenesis and neuropathological presentation and the coexistence of AD and CJD in patients suggest an association between the deposition of the proteolytically processed form of the amyloid precursor protein, B -amyloid (A B ), which deposits in AD, and the abnormal form of the prion protein, PrP Sc , which deposits in sCJD. Methods: We have characterized sCJD patients (n = 14), AD patients (n = 5) and nondemented controls (n = 5) with respect to the deposition of PrP Sc and A B morphologically, biochemically and genetically and correlated these findings to clinical data. Results: sCJD-diseased individuals with abundant deposits of A B present with a specific clinicopathological profile, defined by higher age at disease onset, long disease duration, a genetic profile and only minimal amounts of PrP Sc in the cerebellum. Conclusion: The co-occurrence of pathological changes typical for sCJD and AD in combination with the inverse association between accumulation of A B and PrP Sc in a subgroup of sCJD patients is indicative of common pathways involved in the generation or clearance of A B and PrP Sc in a subgroup of sCJD patients.

In a wide range of dementias, generation and subsequent deposition of abnormally processed proteins is thought to be causally involved in the pathophysiology of the disease and assessment of protein deposition can be employed as a diagnostic tool for the classification of these entities [28]. AD and CJD are two examples of this group of diseases, where generation and deposition of abnormally processed proteins, PrP Sc in the case of sCJD and A B in the case of AD, are involved in the pathophysiology. Coexistence of AD-type neuropathology in sCJD has been repeatedly reported, yet the interpretation of these findings is highly controversial. Some investigators surmise unspecific age-related changes [11] , others assume that this points to similarities in the pathogenesis of AD and CJD [29] . In this study, we characterized deposition of A B in sCJD patients by immunohistochemistry, Western blotting, ELISA and genetic investigations. Using biochemical methods we were able to identify a subgroup of sCJD patients, which is defined by high cerebral A B 42 loads. These patients were on average more than 6 years older than those with minimal or no depos-

its of A B 42 , presented with significantly longer disease durations, were more likely to carry an uncommon polymorphism on PRNP codon 129 or deposit PrP Sc type 2 [30] and had a high likelihood to carry at least one allele of apolipoprotein E e 4. Interestingly, these patients harbor only minimal amounts of PrP Sc in the cerebellum. This clinicopathological signature suggests that this group of patients represents a subgroup of sCJD.

A study focusing on the assessment of genetic profiles of sCJD demonstrated that the apolipoprotein E e 4 allele is an independent risk factor for developing sCJD [31, 32] . In this study, we provide evidence that the apolipoprotein E e 4 status may be linked to the development of a subtype of sCJD. The above-mentioned study did not investigate A B loads in apolipoprotein E e 4-positive sCJD patients. One could hypothesize that patients identified by van Everbroeck et al. [32] belong to the subgroup of sCJD patients characterized by abundant A B and scarce PrP Sc deposits.

A study focusing on the influence of PrP C expression on A B plaque formation suggested that overexpression of PrP C promotes A B plaque formation [15] . Given the fact that PrP C expression is unchanged during the course of prion disease [33] , PrP C upregulation is an unlikely explanation for enhanced A B deposition in certain sCJD patients. Since accumulation of malprocessed proteins in the brain is the result of the differential between its de novo generation and its clearance, it is conceivable that A B deposition in sCJD may be the result of a saturation of common clearance mechanisms [34, 35] . This hypothesis is supported by a wealth of data suggesting that similar processes of protein degradation are in place for PrP Sc and A B [36–38] .

In an attempt to delineate possible molecular pathways explaining the abundant generation of A B 42 in a subset of sCJD patients, we measured central nervous system expression of B -secretase, a key protease for the generation of A B [27] . Several studies have shown that B -secretase activity and protein expression are increased in the cortex of patients suffering from AD [26, 39, 40] . Furthermore, BACE activity seems to be increased in the cerebrospinal fluid of sCJD patients [41] . The fact that we did not find any significant differences in BACE expression is in agreement with published studies and may indicate alternative pathways for A B generation in these patients [41] .

The group of sCJD patients with high cerebral levels of A B 42 showed minimal deposits of PrP Sc . PrP Sc profiling allowed us to directly compare PrP Sc levels between sCJD cohorts [22] . PrP Sc levels showed the most drastic differences in the cerebellum. PrP Sc levels in low A B 42 patients uniformly showed high cerebellar PrP Sc loads, whereas PrP Sc levels in high A B 42 patients uniformly showed low or nondetectable cerebellar PrP Sc levels. Interestingly, cerebellar involvement is a rarity in AD [42] . It has been speculated that the descriptive classification

of AD may camouflage CJD [43] . Although one could argue that the subgroup of sCJD we have identified could have been misdiagnosed as AD, thus supporting the above-mentioned hypothesis, the sCJD typical clinical presentation of these patients argues against the theory that sCJD is commonly misdiagnosed as AD. Taking into account that the majority of cerebral proteinopathies are characterized by deposition of more than one abnormally processed protein [28] , neuropathological diagnosis of dementia should only be carried out in centers equipped to monitor deposition of all disease-associated proteins.

In conclusion, the present study provides evidence for the existence of a subgroup of sCJD characterized by abundant A B 42 deposits, high age at onset of disease, a specific genetic profile and only marginal deposits of PrP Sc . These data are in line with common molecular mechanisms leading to the deposition of A B and PrP Sc . Their delineation will be the focus of future studies. The fact that this newly defined group of patients harbors only minimal amounts of PrP Sc is intriguing. On the one hand, this represents a challenge to neuropathologists, and on the other hand, the possibility that minimal PrP Sc deposits may go undetected could lead to the misdiagnosis of AD.

Since this article does not have an abstract, we have provided the first 150 words of the full text and any section headings.

To the Editor:

In their Research Letter, Dr Gibbons and colleagues1 reported that the annual US death rate due to Creutzfeldt-Jakob disease (CJD) has been stable since 1985. These estimates, however, are based only on reported cases, and do not include misdiagnosed or preclinical cases. It seems to me that misdiagnosis alone would drastically change these figures. An unknown number of persons with a diagnosis of Alzheimer disease in fact may have CJD, although only a small number of these patients receive the postmortem examination necessary to make this diagnosis. Furthermore, only a few states have made CJD reportable. Human and animal transmissible spongiform encephalopathies should be reportable nationwide and internationally.

I lost my mother to hvCJD (Heidenhain Variant CJD). I would like to comment on the CDC's attempts to monitor the occurrence of emerging forms of CJD. Asante, Collinge et al [1] have reported that BSE transmission to the 129-methionine genotype can lead to an alternate phenotype that is indistinguishable from type 2 PrPSc, the commonest sporadic CJD. However, CJD and all human TSEs are not reportable nationally. CJD and all human TSEs must be made reportable in every state and internationally. I hope that the CDC does not continue to expect us to still believe that the 85%+ of all CJD cases which are sporadic are all spontaneous, without route/source. We have many TSEs in the USA in both animal and man. CWD in deer/elk is spreading rapidly and CWD does transmit to mink, ferret, cattle, and squirrel monkey by intracerebral inoculation. With the known incubation periods in other TSEs, oral transmission studies of CWD may take much longer. Every victim/family of CJD/TSEs should be asked about route and source of this agent. To prolong this will only spread the agent and needlessly expose others. In light of the findings of Asante and Collinge et al, there should be drastic measures to safeguard the medical and surgical arena from sporadic CJDs and all human TSEs. I only ponder how many sporadic CJDs in the USA are type 2 PrPSc?

Answering critics like Terry Singeltary, who feels that the U.S. under- counts CJD, Schonberger conceded that the current surveillance system has errors but stated that most of the errors will be confined to the older population.

[In submitting these data, Terry S. Singeltary Sr. draws attention to the steady increase in the "type unknown" category, which, according to their definition, comprises cases in which vCJD could be excluded. The total of 26 cases for the current year (2007) is disturbing, possibly symptomatic of the circulation of novel agents. Characterization of these agents should be given a high priority. - Mod.CP]

Article abstract--Based on 54 demented patients consecutively autopsied at the University of Pittsburgh, we studied the accuracy of clinicians in predicting the pathologic diagnosis. Thirty-nine patients (72.2%) had Alzheimer's disease, while 15 (27.7%) had other CNS diseases (four multi-infarct dementia; three Creutzfeldt-Jakob disease; two thalamic and subcortical gliosis; three Parkinson's disease; one progressive supranuclear palsy; one Huntington's disease; and one unclassified). Two neurologists independently reviewed the clinical records of each patient without knowledge of the patient's identity or clinical or pathologic diagnoses; each clinician reached a clinical diagnosis based on criteria derived from those of the NINCDS/ADRDA. In 34 (63 %) cases both clinicians were correct, in nine (17%) one was correct, and in 11 (20%) neither was correct. These results show that in patients with a clinical diagnosis of dementia, the etiology cannot be accurately predicted during life.

To identify those patients most likely to benefit from a cerebral biopsy to diagnose dementia, we reviewed a series of 14 unselected biopsies performed during a 9-year period (1980 through 1989) at Duke University Medical Center, Durham, NC. Pathognomonic features allowed a definitive diagnosis in seven specimens. Nondiagnostic abnormalities but not diagnostic neuropathologic changes were seen in five additional specimens, and two specimens were normal. Creutzfeldt-Jakob disease was the most frequent diagnosis. One patient each was diagnosed as having Alzheimer's disease, diffuse Lewy body disease, adult-onset Niemann-Pick disease, and anaplastic astrocytoma. We conclude that a substantial proportion of patients presenting clinically with atypical dementia are likely to receive a definitive diagnosis from a cerebral biopsy. However, in those with coexisting hemiparesis, chorea, athetosis, or lower motor neuron signs, cerebral biopsies are less likely to be diagnostic. (Arch Neurol. 1992;49:28-31)

"Dementia" is a syndrome characterized by global deterioration of cognitive abilities and is the general term used to describe the symptom complex of intellectual deterioration in the adult. It is associated with multiple causes, although Alzheimer's disease (AD) alone accounts for approximately 60% of cases.1-3...

One of our papers (in Alzheimer's Disease Related Disord. 3:100-109, 1989) in text cites 6 of 46 (13%) of clinical AD as CJD. There may be a later paper from another lab showing the same higher than expected incidence but I can't put my hands on it right now. We also have a lot of papers from 1985 on stating that there are likely many silent (non-clinical) CJD infections, i.e. much greater than the "tip of the iceberg" of long standing end-stage cases with clinical symptoms. Hope this helps.